tbuckley/cabot-search huggingface dataset:
Abstract P2-11-02: BIOMARKERS RELATED TO SURVIVAL BENEFIT IN THE TREATMENT OF METASTATIC LUMINAL BREAST CANCER (mBC) WITH CYCLIN 4/6 INHIBITORS (CDK 4/6i) PLUS ENDOCRINE THERAPY (ET)
Authors: Serafin Morales Murillo, Ariadna Gasol Cudós, Noemí Tuset Der-Abrain, Izaskun Urdanibia, Alvaro Rodriguez Galindo, Ana Velasco Sánchez, Felip Vilardell Villellas, Douglas Sánchez Guzmán, Carles Canosa Morales, Jordi Melé Olivé, Laura Arbones Cid
Journal: Cancer Research (2023)

Abstract Treatment with CDK4/6i plus ET is the standard treatment for mBC with a significantly better progression free survival (PFS) and a long treatment duration response, although there’s finally a progression. The expression of cyclin E and progesterone receptor had been related to survival, so analyzing of these potential biomarkers could help to select their effect in patients with a long treatment duration (&amp;gt; 20 months). We evaluate 68 mBC treated with CDK4/6I plus ET as a clinical practice in a single institution. Median age was 68 years, 27(39,7%) patients had de novo metastatic disease, 17 (25%) progressed during ET adjuvant, and 24 (35,3%) progressed after 5 years of ET. Forty-eight patients (70%) received CDK4/6I plus ET in first line and visceral disease was present in 40% of patients. The median expression by histoscore with immunohistochemistry of cyclin E (CycE) was 75,3 (4-97) and progesterone receptor (PR) 121. Median PFS was 16 months (8,3- 23,6) with 45 events, 25 months in patients treated in first line and 12 months in second line (p: 0,0001). We analyzed 59 patients who had already completed CDK4/6I plus ET or had achieved a PFS more than 20 months, 40 (69%) in first line and 18 (31%) in second line. We summarized the related of expression of PR, CycE and this combination with PFS more than 20 month. CONCLUSION: Treatment with CDK4/6i plus ET achieved long treatment duration in patients with low expression of cyclin E (OR 3,1 p:0,045), positive progesterone receptor (OR 3,89 p: 0023) and specially in patients with positive progesterone receptor and low expression of cyclin E (OR 7,22 p:0,016). Patients with negative progesterone receptor and high expression of cyclin E had a poor prognosis with a median disease-free survival of 6 months (2.8 – 9.2), so these patients required other treatment approaches to improve their outcomes. Table Citation Format: Serafin Morales Murillo, Ariadna Gasol Cudós, Noemí Tuset Der-Abrain, Izaskun Urdanibia, Alvaro Rodriguez Galindo, Ana Velasco Sánchez, Felip Vilardell Villellas, Douglas Sánchez Guzmán, Carles Canosa Morales, Jordi Melé Olivé, Laura Arbones Cid. BIOMARKERS RELATED TO SURVIVAL BENEFIT IN THE TREATMENT OF METASTATIC LUMINAL BREAST CANCER (mBC) WITH CYCLIN 4/6 INHIBITORS (CDK 4/6i) PLUS ENDOCRINE THERAPY (ET) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-02.
Abstract P1-13-23: Carboplatin resistance-associated changes in the 3D chromatin landscape of a triple-negative breast cancer Patient-Derived Xenograft
Authors: Mikhail Dozmorov, Maggie Marshall, Narmeen Rashid, Jacqueline Grible, Aaron D. Valentine, Amy Olex, Kavita Murthy, Abhijit Chakraborty, Joaquin Reyna, Daniela Salgado Figueroa, Da-Inn Lee, Brittany Baur, Sushmita Roy, Ferhat Ay, Chuck Harrell
Journal: Cancer Research (2023)

Abstract Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. Cancer-associated copy number variants and single nucleotide polymorphisms promote rewiring of chromatin loops, disruption of topologically associating domains (TADs), active/inactive chromatin state switching, leading to oncogene expression and silencing of tumor suppressors. However, little is known about 3D changes during cancer progression to a chemotherapy-resistant state. We integrated chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing obtained from triple-negative breast cancer patient-derived xenograft primary tumors (UCD52) and carboplatin-resistant samples and found increased short-range (&amp;lt; 2Mb) interactions, chromatin looping, formation of topologically associating domains (TAD), chromatin state switching into a more active state, and amplification of ATP-binding cassette (ABC) transporters. Transcriptome changes suggested the role of long-noncoding RNAs in carboplatin resistance. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of aggressiveness-, metastasis- and other cancer-related pathways. Integrative analysis highlighted increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial energy metabolism. Our results suggest that 3D genome remodeling may be a key mechanism underlying carboplatin resistance. Citation Format: Mikhail Dozmorov, Maggie Marshall, Narmeen Rashid, Jacqueline Grible, Aaron D. Valentine, Amy Olex, Kavita Murthy, Abhijit Chakraborty, Joaquin Reyna, Daniela Salgado Figueroa, Da-Inn Lee, Brittany Baur, Sushmita Roy, Ferhat Ay, Chuck Harrell. Carboplatin resistance-associated changes in the 3D chromatin landscape of a triple-negative breast cancer Patient-Derived Xenograft [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-23.
Abstract P2-26-09: Synergistic activity of PI3K inhibitor in combination with AZD6738, ATR inhibitor in breast cancer preclinical model via DNA damage response pathway
Authors: Yong Wha Moon, Mithun Gosh, Nahee Park, Kamal Pandey, Nar Bahadur Katwal, Sa Deok Hong
Journal: Cancer Research (2023)

Abstract Background: The PI3K inhibition has been an appealing approach for anticancer therapy due to its crucial role in cell growth, proliferation, and survival in various cancers. Emerging data suggest the PI3K pathway is also involved in DNA replication and genome stability, making DNA damage response (DDR) inhibitors as an attractive combination treatment for PI3K pathway blockades. Here, to enhance the efficacy of PI3K inhibitors, we investigated the novel approach combining PI3K inhibitors (alpelisib, AZD8835, AZD8186, NVP-BKM120) with DDR blockade using ATR inhibitor (AZD6738) in breast cancer preclinical models. Methods: Hormone receptor-positive breast cancer cells, MCF7 (PIK3CA E545K mutation) and T47D (PIK3CA H1047R mutation) were used. First, cell viability and the synergistic effect of combination drug was carried out by MTT assy. Next, western blot, cell cycle analysis, apoptosis assay, and immunocytochemistry were conducted to validate the hypothesis. Finally, tumor xenograft experiments were conducted using BALB/c nude mice to validate the in vitro data. Results: A synergistic antiproliferative effect was observed over a wide range of combination (PI3K inhibitor + ATR inhibitor) concentrations (even in a lower concentration as 1/10 x IC50) in vitro, suggesting that when alpelisib is combined with an ATR inhibitor, there may be possibility of lowering the effective dosage of alpelisib. After confirmation of the strong synergistic effect in sub-G1/G0-G1 arrest-mediated apoptosis by the combination treatment, we demonstrated that expressions of phospho ATR, ATM, and CHK1 were suppressed but -H2AX markedly increased by combination treatment as compared to PI3K inhibitors and ATR inhibitor alone. This suggests that combination treatment activates apoptotic pathway through enhanced DNA double strand breaks. Finally, the in vivo study showed that the combination treatment group tended to show a greater tumor growth inhibition compared with PI3K inhibitor or ATR inhibitor alone. Conclusion: The combined inhibition of PI3K and ATR showed a synergistic anticancer effect in vitro and in vivo. ATR inhibitor in combination with PI3K inhibitor merits further clinical investigation to enhance the activity of PI3K inhibitor for the treatment of PIK3CA mutated breast cancer patients. Citation Format: Yong Wha Moon, Mithun Gosh, Nahee Park, Kamal Pandey, Nar Bahadur Katwal, Sa Deok Hong. Synergistic activity of PI3K inhibitor in combination with AZD6738, ATR inhibitor in breast cancer preclinical model via DNA damage response pathway [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-09.
Abstract P1-09-07: Omission of Axillary Surgery for Ipsilateral Breast Tumor Recurrence with Negative Nodes after Previous Breast-Conserving Surgery: Is It Oncologically Safe?
Authors: Feilin Qu, Caijin Lin, Jun-Jie Li, Zhi-Ming Shao
Journal: Cancer Research (2023)

Abstract Background: Salvage mastectomy is traditionally recommended for patients who developed ipsilateral breast tumor recurrence (IBTR) in light of the previous breast irradiation. However, it remains controversial whether surgical axillary staging (SAS) is necessary for IBTR patients with negative nodes. This study aimed to evaluate the oncologic safety of omitting SAS for IBTR. Methods: We retrospectively identified patients who developed invasive IBTR with negative nodes after undergoing breast-conserving surgery (BCS). Patterns of care in nodal staging were analyzed based on prior axillary staging status. Clinicopathologic characteristics and adjuvant treatment of the initial tumor, as well as the IBTR, were compared between SAS and no SAS groups. Kaplan-Meier method and Cox regression model were utilized to compare the loco-regional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates after IBTR removal between the two groups. Results: A total of 154 IBTR patients were eligible for final analysis. Compared to no SAS group, SAS group was less likely to undergo ALND (15.1% vs 73.3%, p &amp;lt; 0.001) at initial BCS, had a longer recurrence interval (2.8 vs 2.1 years, p=0.03), and were more likely to have discordant molecular subtype with primary tumor (35.8% vs 12.9%, p=0.001). However, the extent of axillary staging did not affect systemic or radiation recommendations. In the subgroup of patients without previous ALND, the clinicopathologic characteristics were roughly comparable. Pathologic analysis revealed pathologically uninvolved nodal status in approximately 85% of patients receiving SAS at time of IBTR in the overall population and the subgroup (Table 1). No significant differences were observed in LRRFS, DMFS and OS between the two groups (Table 2). Conclusion: For node-negative IBTR patients, we observed selection bias on the basis of prior ALND, shorter recurrence interval, and concordant molecular subtype favoring no SAS, but comparable LRRFS, DMFS, and OS. These results support wider consideration of sparing SAS in the management of IBTR, especially in patients without previous ALND. Table 1. Pathologic axillary staging in patients receiving axillary surgery at time of IBTR. Table 2. Cox regression analysis of LRRFS, DMFS, and OS after IBTR. Citation Format: Feilin Qu, Caijin Lin, Jun-Jie Li, Zhi-Ming Shao. Omission of Axillary Surgery for Ipsilateral Breast Tumor Recurrence with Negative Nodes after Previous Breast-Conserving Surgery: Is It Oncologically Safe? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-07.
Abstract P1-09-11: Impact of breast surgical procedure on survival in BRCA mutated patients with invasive breast cancer: mastectomy versus conservative treatment
Authors: CLEMENTINE JANKOWSKI, Katia Mahiou, Vincent Laura, Hélène Costaz, Marie-Martine padéano, Sylvain Causeret, Ariane Mamguem, Sandrine Dabakuyo, CHARLES COUTANT
Journal: Cancer Research (2023)

Abstract Introduction: Patients with BRCA1/2 mutations have a higher risk of developing breast cancer compared to the wild-type population. For patients with a BRCA mutation, there are no specific recommendations for surgical management. The aim of this study was therefore to retrospectively investigate overall survival (OS) and recurrence-free survival (RFS) of BRCA mutated patients with localized invasive breast cancer, by comparing conservative surgery versus mastectomy. Methods: This study was based on data from the Côte d’Or breast and gynecological cancer registry. Data from patients with a constitutional BRCA1/2 mutation who presented with invasive breast cancer were collected retrospectively from 1998 to 2018. The Kaplan-Meier method was used to describe RFS and OS. Results:A total of 104 patients were included in the analysis, of whom 69 had conservative surgery and 35 underwent mastectomy. Regarding survival, there was no significant difference in OS (HR =1.49; 95% confidence interval (CI) [0.76-2.93], p=0.25). Similarly, there was no significant difference in RFS (HR =1.40; 95% CI [0.81-2.40], p=0.22), survival without homolateral recurrence (HR =0.88; 95% CI [0.30-2.61], p=0.89), without contralateral recurrence (HR =1.50; 95% CI [0.55-4.09], p=0.42), or without distant metastatic recurrence (HR =1.42, 95% CI [0.69-2.90], p=0.33). Conclusion: In invasive breast cancer in a patient with a germline BRCA1/2 mutation, conservative surgery, when possible, appears to be a feasible option over total mastectomy, with no difference in overall survival. However, the patient should be informed of the aggressive nature of recurrence in this population requiring chemotherapy in most cases. Citation Format: CLEMENTINE JANKOWSKI, Katia Mahiou, Vincent Laura, Hélène Costaz, Marie-Martine padéano, Sylvain Causeret, Ariane Mamguem, Sandrine Dabakuyo, CHARLES COUTANT. Impact of breast surgical procedure on survival in BRCA mutated patients with invasive breast cancer: mastectomy versus conservative treatment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-11.
Abstract P6-14-05: Regulation of cellular identity and spatial organization during collective breast cancer invasion
Authors: Andrea E. Doak, Kevin J. Cheung
Journal: Cancer Research (2023)

Abstract An early step in breast cancer progression is invasion of tumor cells into surrounding tissues. In many breast cancers, particularly ductal carcinomas, this invasion is accomplished by tumor cells migrating as a cohesive group. This often involves cells that take on heterogeneous roles as either leader or follower cells. While studies in common mouse and human breast cancer models have established that leader cells express high levels of keratin-14 (K14) and other basal epithelial markers, the molecular mechanisms regulating K14+ leader cell identity remain obscure. Here we performed time-sampled single cell RNA-sequencing in 3D type I collagen-embedded tumor organoids isolated from the MMTV-PyMT luminal B model of breast cancer. 11 distinct cellular transcriptional states were identified and correlated with K14 expression and invasive strand formation. Having identified the leader cell state we next asked what transcription factors were enriched, reasoning that transcription factors could be master regulators of leader cell fate. 30 different shRNAs targeting 10 genes were systematically evaluated for their effects on collective invasion. From this screen, suppression of Hes1, the downstream target of Notch signaling, yielded a marked switch from collective to single cell invasion. Disseminating single tumor cells maintained high expression of K14 in Hes1 knockdown organoids which was phenocopied by gamma-secretase inhibition in a human TNBC PDX model. Because K14+ tumor cells highly express the Notch ligand Jag1, these results support a model in which Notch signaling, specifically through activation of Hes1, dictates leader cell identity and spatial organization during collective invasion. Studies are ongoing investigating the impact of Hes1 dynamics on leader cell adhesion, hybrid EMT state, and preference for single versus collective metastasis. Because Notch suppression induces leader cell dissemination, we propose that Notch targeted therapy should be combined with therapies eradicating leader cells. Citation Format: Andrea E. Doak, Kevin J. Cheung. Regulation of cellular identity and spatial organization during collective breast cancer invasion. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-14-05.
Efficacy, Safety, and Biomarker Analysis of Neoadjuvant Camrelizumab and Apatinib in Patients With Resectable NSCLC: A Phase 2 Clinical Trial
Authors: Jun Zhao, Liang Zhao, Wei Guo, Shuhang Wang, Xiuli Tao, Lin Li, Yousheng Mao, Fengwei Tan, Yushun Gao, Ning Wu, Jianming Ying, Qi Xue, Ning Li, Shugeng Gao, Jie He
Journal: Journal of Thoracic Oncology (2023)
Abstract P1-10-16: Cardiac conduction system exposure with modern radiotherapy techniques for breast cancer irradiation
Authors: Pierre Loap, Farid Goudjil, Ludovic De Marzi, Vincent Servois, Krassen Kirov, Alain Fourquet, Youlia M. Kirova
Journal: Cancer Research (2023)

Abstract Introduction: Exposition of cardiac conduction system during breast radiotherapy has never been studied, despite increasing use of intensity modulated radiotherapy which expose larger volume to low dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arctherapy (VMAT) and estimated the potential dosimetric benefit with intensity modulated protontherapy (IMPT). Materials and methods: Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation CT scans of twelve breast cancer patients having undergone conserving surgery and adjuvant locoregional VMAT. IMPT treatment was re-planned on the simulation CT scans for all breast cancer patients. Mean and maximum doses to the SAN and the AVN were retrieved and compared. Correlation coefficients were calculated between doses to the SAN or the AVN and to the whole heart. Results: Average mean doses to the SAN and to the AVN were 2.8 Gy and 2.3 Gy respectively for left-sided irradiation and 9.6 Gy and 3.6 Gy respectively for right-sided irradiation. Average maximum doses to the SAN and to the AVN were 3.5 Gy and 2.8 Gy respectively for left-sided irradiation and 13.1 Gy and 4.6 Gy respectively for right-sided irradiation. IMPT significantly reduces doses to conduction nodes. Correlations between doses to the SAN or the AVN and the whole heart were usually significant. Conclusion: SAN and AVN can be substantially exposed during breast VMAT, especially for right-sided irradiation. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac sparing techniques, such as respiratory techniques or proton therapy, which could be beneficial to patients with underlying rhythmic or conduction disorders. Citation Format: Pierre Loap, Farid Goudjil, Ludovic De Marzi, Vincent Servois, Krassen Kirov, Alain Fourquet, Youlia M. Kirova. Cardiac conduction system exposure with modern radiotherapy techniques for breast cancer irradiation [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-16.
Abstract P1-11-18: The efficacy and safety of trastuzumab and pertuzumab in combination with different chemotherapy regimens for neoadjuvant treatment of HER2-posotive breast cancer: a multi-center real-world study in China
Authors: Xiaowei Qi, Hong Hu, chen wenlin, xu yan, liu shu, fang yanman, Taolang Li, ming jia, zhou sihai, chai fan, liang yueyang, fan yuanming, Yi Zhang, Peng Tang, jiang jun, nie jianyun, Li Chen, Shushu Wang
Journal: Cancer Research (2023)

Abstract Background: Dual HER2 targeted therapy with trastuzumab (H) and pertuzumab (P) has been approved as neoadjuvant therapy for patients with HER2-positive breast cancer in China in 2019 based on the results from NeoSphere and PEONY study. However, the real-world efficacy and safety data are currently lack of evidence in China. Therefore, this multi-center real-world study aims to retrospectively analyze the efficacy and safety of neoadjuvant trastuzumab and pertuzumab combined with different chemotherapy regimens of HER2-positive early breast cancer. Methods: Patients received trastuzumab and pertuzumab in combination with different chemotherapy regimens, including taxanes (T), cyclophosphamide (C), anthracyclines (A) were collected retrospectively from 12 centers. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate. Results: A total of 357 patients were enrolled, among which 204 (57.5%) recieved TCbHP, 92 (25.9%) recieved EC-THP, and 51 (14.4%) received THP as chemotherapy regimens. The median age was 48 years old (range, 22-76), 142 (39.8%) of patients were classified as hormone receptor (HR)-positive, and 215 (60.2%) were HR-negative. The overall tpCR rate was 58.5% (95%CI, 53.2%-63.7%). tpCR rate for HR-negative patients was significantly higher than HR-positive patients (65.6% vs. 47.9%, p=0.001) and there was not any statistical difference according to chemotherapy regimens (56.9% for TCbHP, 56.5% for EC-THP, and 66.7% for THP, p=0.445). The most common adverse events included anemia (40.1%), white blood cell count decreased (34.3%), ejection fraction decreased (19.5%), Alanine aminotransferase increased (18.9%), platelet count decreased (12.8%) and neutrophil count decreased (12.0%). There was not any toxicity leading to death. Conclusions: Multi-center real-world data show satisfactory tpCR rate and tolerable adverse events of trastuzumab and pertuzumab in combination with different chemotherapy regimens in China. Citation Format: Xiaowei Qi, Hong Hu, chen wenlin, xu yan, liu shu, fang yanman, Taolang Li, ming jia, zhou sihai, chai fan, liang yueyang, fan yuanming, Yi Zhang, Peng Tang, jiang jun, nie jianyun, Li Chen, Shushu Wang. The efficacy and safety of trastuzumab and pertuzumab in combination with different chemotherapy regimens for neoadjuvant treatment of HER2-posotive breast cancer: a multi-center real-world study in China [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-18.